Despite the availability of public health interventions for their prevention and control, in 2011 the CDC estimated 14.1 million new cases of human papillomavirus (HPV) and 2.86 million new cases of Chlamydia trachomatis (CT) infection in the US. While both infections are asymptomatic in most women, they can have serious health consequences including cancer, pre-term pregnancy outcomes, pelvic inflammatory disease, ectopic pregnancy and infertility. The greatest promise for progress in reducing the burden of HPV and CT will result from integration of evaluation of current prevention and control measures with basic research designed to understand limitations to current strategies and adapt new technologies and information for continuous evidence-based improvement in outcomes. The specific aims of this Sexually Transmitted Infection Cooperative Research Center (STI-CRC) application are to (1) expand the scope of the current University of New Mexico (UNM) STI-CRC by establishing the Epidemiology and Prevention Interdisciplinary Center for Sexually Transmitted Infections (EPIC-STI), a center with a focus on HPV and CT infections that incorporates cooperative multidisciplinary research approaches to address key gaps in the knowledge required to reduce the burden of preventable or treatable sexually transmitted infections, (2) fund and support 4 integrated and inter-disciplinary projects that (a) elucidate th details of the development of CD4+ T-cell protective immunity against CT infection of the genital tract, (b) utilize novel virus-display technology to develop vaccine strategies for the durable and effective prevention of HPV and CT infection, (c) use mixed design approaches to characterize the burden of sexually transmitted infection and co-infection in the population as well as the within- and between woman variability of host response to CT infection, and (d) employ unique health informatics systems to delineate the effectiveness of HPV vaccination and evolving cervical cancer screening practices on the burden of STIs and their associated disease outcomes using population-based approaches; 3) Establish two cores that support the EPIC-STI trans-disciplinary research approaches and; 4) contribute to building the next cadre of STI researchers through mentorship and developmental research projects.